A multifunctional triblock copolymer intended for targeted drug delivery applications has been designed and successfully synthesized. Following various controlled polymerization and modification steps, a saccharide end-functionalized polyoxyethylene block was attached through an aromatic imine bond, cleavable in slightly acidic conditions, to an amphiphilic diblock copolymer comprising a biodegradable hydrophobic block and a partially modified with mitochondria targeting ligands polycationic block. The micelles formed from the triblock copolymer in aqueous media possess key functions (cleavable "stealth" shield, targeting groups) needed for safe extracellular transport, successful cell internalization, and drug delivery to the target cellular organelles. The multifunctional nanocarriers were loaded with the plant-derived anticancer drug curcumin, and in vitro analyses revealed that their cytotoxic, apoptogenic, and NF-κB-inhibitory effects on target cells were superior over those of the free drug and non-functionalized polymer micelles of similar composition. Moreover, the enhanced cellular internalization and mitochondrial accumulation of the multifunctional nanocarriers compared to their non-functionalized analogues was visualized by fluorescence microscopy. The results indicate that the presented multifunctional micelles have a potential for application in nanomedicine for enhanced organelle-specific drug delivery.
Keywords: dual-targeting; multifunctional; pH-sensitive; polymer nanocarrier.